Role of SIRT6 in the pancreatic beta cell aging

SIRT6在胰腺β细胞衰老中的作用

• 批准号: 10371337
• 负责人: X Charlie Dong
• 金额: $ 23.78万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10371337
• 关键词: Age; Age-Years; Aging; B Cell Proliferation; B-Cell Development; Beta Cell; Biological Process; Calcium Signaling; Cell Aging; Cell Death; Cell membrane; Cell physiology; DNA Damage; Data; Deacetylase; Defect; Development; Diabetes Mellitus; Diet; Disease; Epigenetic Process; Female; Gene Expression; Gene Expression Regulation; General Population; Genes; Glucose; Glucose Intolerance; Guanosine Triphosphate Phosphohydrolases; HDAC4 gene; Histologic; Homeostasis; Human; Impairment; Insulin; Intervention; Islets of Langerhans; Knock-out; Knockout Mice; Knowledge; Life; Literature; Longevity; Metabolic; Metabolism; Mission; Mitochondria; Modeling; Molecular and Cellular Biology; Monitor; Monomeric GTP-Binding Proteins; Mus; Non-Insulin-Dependent Diabetes Mellitus; Oxidative Stress; Persons; Phenotype; Physiological; Physiology; Play; Population; Premature Mortality; Prevalence; Prevention; Process; Proteins; Public Health; Regulation; Research; Risk Factors; Role; Sirtuins; Structure of beta Cell of islet; Testing; Transgenes; Transgenic Mice; United States National Institutes of Health; age related; anti aging; base; blood glucose regulation; burden of illness; cell age; cell injury; diabetes pathogenesis; epigenetic regulation; expectation; gene function; glucose metabolism; high risk; human old age (65+); improved; innovation; insight; insulin secretion; male; middle age; molecular phenotype; mouse model; new therapeutic target; novel; overexpression; therapeutic development; transgene expression; voltage

Project Summary During aging, pancreatic beta cells undergo a decline in insulin secretion capacity, and this contributes to nearly 3-fold high diabetes prevalence in people aged over 65 years compared to the general population. Sirtuin 6 (SIRT6), a histone deacetylase, has been suggested to be a longevity factor. In the preliminary study, we have demonstrated that SIRT6 is required to maintain normal beta cell function and SIRT6 is downregulated in the beta cells during aging. Therefore, we hypothesize that SIRT6 plays an important role in the protection of pancreatic beta cells against aging-associated cellular damage. In this application, we will investigate the SIRT6 function and mechanism in the regulation of pancreatic beta cell aging. It is our expectation that the findings from this project will advance our understanding of the fundamental process of the aging of pancreatic beta cells and provide potential novel targets for the development of prevention and treatment of the age-related diabetes.

项目总结